Mechanisms of Actinidia chinensis Planch roots in the treatment of breast cancer based on network pharmacology and molecular docking.

This study explores the mechanisms by which the root of Actinidia chinensis Planch (ACP) may exert therapeutic effects on breast cancer (BC), using network pharmacology and molecular docking techniques. Active compounds in ACP root were screened using the Traditional Chinese Medicine Systematic Pharmacology database (oral bioavailability ≥ 30%, drug-likeness ≥ 0.18%), and potential targets were predicted via the PharmMapper database (normalized fit score ≥ 0.6). BC-related targets were retrieved from GeneCards, DisGeNet, OMIM, DrugBank, and TTD databases. Common targets were identified using Venny 2.1 and imported into STRING 11.0 to construct a protein-protein interaction network with a confidence score ≥ 0.4. Visualization and topological analysis were conducted using Cytoscape 3.9.1. Core compounds were identified based on degree, betweenness centrality, and closeness centrality, while core targets were determined using the maximum clique centrality method. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were performed via the Metascape platform. Molecular docking validation was carried out using AutoDock Tools 1.5.7 and AutoDock Vina 1.1.2, with docking results visualized using PyMOL. A total of 14 active compounds and 184 potential targets were identified from ACP root, along with 9418 potential BC-related targets. Among them, 158 overlapping targets were identified. Ten key targets and 8 key compounds were ultimately selected. Molecular docking results revealed that the binding energies between key compounds and targets ranged from -5.8 to -9.9 kcal/mol, with the strongest interaction- observed between maslinic acid and GSK3-B (-9.9 kcal/mol). Gene ontology enrichment analysis indicated involvement in biological processes such as hormone stimulus response, protein phosphorylation, and enzyme activity regulation; cellular components including intracellular secretory granules and the cell membrane; and molecular functions such as kinase activity, nuclear receptor binding, and ligand-activated transcription regulation. Kyoto encyclopedia of genes and genomes analysis showed significant enrichment in cancer-related pathways and key signaling networks, suggesting roles in tumor progression and cell proliferation/survival. This study suggests that maslinic acid and oleanolic acid from ACP root may treat breast cancer by targeting GSK3β and EGFR, affecting MAPK, PI3K-Akt, and ROS pathways. Further validation in in vivo and in vitro models is needed.